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Papers of the Week


Papers: 15 Apr 2023 - 21 Apr 2023

RESEARCH TYPE:
Basic Science


Animal Studies, Molecular/Cellular, Neurobiology

PAIN TYPE:
Psychological/Comorbidities


2023 Apr 17


Nat Commun


37069246


14


1

Editor's Pick

Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice.

Authors

Ji YW, Shen ZL, Zhang X, Zhang K, Jia T, Xu X, Geng H, Han Y, Yin C, Yang JJ, Cao JL, Zhou C, Xiao C

Abstract

Nucleus- and cell-specific interrogation of individual basal forebrain (BF) cholinergic circuits is crucial for refining targets to treat comorbid chronic pain-like and depression-like behaviour. As the ventral pallidum (VP) in the BF regulates pain perception and emotions, we aim to address the role of VP-derived cholinergic circuits in hyperalgesia and depression-like behaviour in chronic pain mouse model. In male mice, VP cholinergic neurons innervate local non-cholinergic neurons and modulate downstream basolateral amygdala (BLA) neurons through nicotinic acetylcholine receptors. These cholinergic circuits are mobilized by pain-like stimuli and become hyperactive during persistent pain. Acute stimulation of VP cholinergic neurons and the VP-BLA cholinergic projection reduces pain threshold in naïve mice whereas inhibition of the circuits elevated pain threshold in pain-like states. Multi-day repetitive modulation of the VP-BLA cholinergic pathway regulates depression-like behaviour in persistent pain. Therefore, VP-derived cholinergic circuits are implicated in comorbid hyperalgesia and depression-like behaviour in chronic pain mouse model.